title: Differentiation syndrome in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline chemotherapy: characteristics, outcome, and prognostic factors.
abstract: Differentiation syndrome (DS) can be a life-threatening complication in patients with acute promyelocytic leukemia (APL) undergoing induction therapy with all-trans retinoic acid (ATRA). Detailed knowledge about DS has remained limited. We present an analysis of the incidence, characteristics, prognostic factors, and outcome of 739 APL patients treated with ATRA plus idarubicin in 2 consecutive trials (Programa Español de Tratamientos en Hematología [PETHEMA] LPA96 and LPA99). Overall, 183 patients (24.8%) experienced DS, 93 with a severe form (12.6%) and 90 with a moderate form (12.2%). Severe but not moderate DS was associated with an increase in mortality. A bimodal incidence of DS was observed, with peaks occurring in the first and third weeks after the start of ATRA therapy. A multivariate analysis indicated that a WBC count greater than 5 x 10(9)/L and an abnormal serum creatinine level correlated with an increased risk of developing severe DS. Patients receiving systematic prednisone prophylaxis (LPA99 trial) in contrast to those receiving selective prophylaxis with dexamethasone (LPA96 trial) had a lower incidence of severe DS. Patients developing severe DS showed a reduced 7-year relapse-free survival in the LPA96 trial (60% vs 85%, P = .003), but this difference was not apparent in the LPA99 trial (86% vs 88%).
authors.affiliation: Hospital Universitario La Fe, Valencia, Spain.
authors.forename: Pau
authors.initials: P
authors.lastname: Montesinos
authors.forename: Juan M
authors.initials: JM
authors.lastname: Bergua
authors.forename: Edo
authors.initials: E
authors.lastname: Vellenga
authors.forename: Chelo
authors.initials: C
authors.lastname: Rayón
authors.forename: Ricardo
authors.initials: R
authors.lastname: Parody
authors.forename: Javier
authors.initials: J
authors.lastname: de la Serna
authors.forename: Angel
authors.initials: A
authors.lastname: León
authors.forename: Jordi
authors.initials: J
authors.lastname: Esteve
authors.forename: Gustavo
authors.initials: G
authors.lastname: Milone
authors.forename: Guillermo
authors.initials: G
authors.lastname: Debén
authors.forename: Concha
authors.initials: C
authors.lastname: Rivas
authors.forename: Marcos
authors.initials: M
authors.lastname: González
authors.forename: Mar
authors.initials: M
authors.lastname: Tormo
authors.forename: Joaquín
authors.initials: J
authors.lastname: Díaz-Mediavilla
authors.forename: Jose D
authors.initials: JD
authors.lastname: González
authors.forename: Silvia
authors.initials: S
authors.lastname: Negri
authors.forename: Elena
authors.initials: E
authors.lastname: Amutio
authors.forename: Salut
authors.initials: S
authors.lastname: Brunet
authors.forename: Bob
authors.initials: B
authors.lastname: Lowenberg
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Sanz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012008:Recurrence; D012307:Risk Factors; D013577:Syndrome; D013997:Time Factors; D014212:Tretinoin / Q000627:therapeutic use*
chemical_list: D018943:Anthracyclines; D014212:Tretinoin